1997 Fiscal Year Final Research Report Summary
Roles of TNF and leptin, the ob gene product, in genetic obesity.
| Project/Area Number |
08671179
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内分泌・代謝学
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| Research Institution | Jichi Medical School, Faculty of Medicine |
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Principal Investigator |
KAWAKAMI Masanobu Jichi Medical School, Professor Faculty of Medicine, 医学部, 教授 (40161286)
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| Co-Investigator(Kenkyū-buntansha) |
SODA Kuniyasu Jichi Medical School, Assistant Faculty of Medicine, Professor, 医学部, 講師 (00221341)
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| Project Period (FY) |
1996 – 1997
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| Keywords | TNF / obesity / cachexia / appetite |
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| Research Abstract |
The final goal of this study was to elucidate the roles of TNF,its related cytokines and leptin in the development of obesity with genetic basis in metabolism. TNF or IL-1 which is known to have many of common biological activities with TNF was administered to animal models with different causes, ob/ob mouse and the goldthioglucose induced obesity mouse. The former is genetic obesity and the latter is chemicall induced obesity by chemical destroy of satiety center. The increase of body weight was parallel to the increase of food intake in ob/ob mouse as well as experimentally induced obesity mouse. TNF was expressed in subcutaneous and visceral fat but not in muscle in ob/ob mouse. Fat tissue in ob/? mouse did not express the cytokine suggesting TNF expression in fat is causative for obesity. However, exogenously administered TNF induced marked reduction of body weight in both genetic and chemically induced obesity mouse. In KKA mouse, moderately obese mouse of poylgenic origin, the increase of body weight was significantly affected by the ratio of n-3, n-6 polyunsaturated and saturated fatty acids which also influenced the serum levels of leptin. TNF expression in fat tissue of these mice is now being analyzed.
In order to supplement the study, the effect of IL-10 gene therapy on weight reduction in colon 26 transplanted mouse, the expression of cytokines in several tissues by various stimuli, and the effect of cytokines on the function of various tissues were also studied.
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